Immunochemical techniques have been used to verify our concepts relating to macromolecular binding of biologically important, small substrate molecules. The latter include drugs (eg. morphine, delta 9- THC and other cannabinoids) and steroids (eg. estriol, estradiol). Highly specific assay systems (fluorescence and isotopes) have been and are being developed to quantitate each native substrate in body fluids. Using these sensitive radioimmune techniques delta 9-THC and carboxy-THC levels in plasma urine and saliva of chronic and occasional marihuana users are being measured. Though assay sensitivities are limited by low specific activity, non homologous markers they are still sufficient to quantitate delta 9-THC and carboxy THC in plasma, 1 - 6 hours after smoking a single marihuana cigarette. Greater sensitivity is expected with the high specific activity, homologous markers under development. Extensions from native drugs and endocrines to their significant metabolites (eg. morphine-3-glucuronide, estriol-16-glucuronide) have given rise to antisera which were used for direct body fluid metabolite assays. A limited program is also under way to study in vivo alterations of native drugs and consequent physiological effects induced by active and passive immune techniques. Bibliographic references: Gross, S.J., Grant, J.D., Wong, S.L.R., Lomax, P. and Campbell, D.H.: Critical antigenic determinants for production of antibody to distinguish morphine from heroin, codeine and dextromethorphan. Immunochemistry 11: 453 (1974). Gross, S.J., Soares, J.B., Wong, S.L.R., and Schuster, R.E.: Marihuana metabolites measured by a radioimmune technique. Nature 252 581(1974).